Abstract SY37-03: Leveraging the complexities of tumor associated macrophages for effective anti-cancer therapy

Abstract Macrophages are innate immune cells that play a critical role in host defense and maintaining tissue homeostasis, however their infiltration into tumors is associated with disease progression and resistance to therapy. Tumor associated macrophages (TAMs) represent a significant proportion of solid tumors, including breast cancer. TAMs play a major role in tumorigenesis as they can enhance tumor cell growth, angiogenesis and metastasis. In addition, TAMs can inhibit anti-tumor responses of T cells. Our recent work has shown that removal or conversion of TAMs to an anti-tumor phenotype enhances chemo- and immuno-therapy establishing TAMs as targets for anti-cancer therapy. Using high-dimensional single-cell and multi-omics profiling of murine and human breast tumors we reveal multiple subsets of TAMs with distinct transcriptional and activity profiles that correlate with progression of disease and response to therapy. This work has revealed the complexity of TAMs and major gaps in our knowledge of the functional and phenotypic characterization of TAM subsets associated with cancer, before and after treatment. Here we will discuss the complexity of TAMs in solid tumors including characterizing TAM subsets, location, and crosstalk with neighboring cells, as well as novel TAM-modulating strategies and combinations that are likely to enhance current therapies and overcome chemo- and immuno-therapy resistance. Our findings support the idea that targeting TAMs offers great potential to enhance both chemo- and immuno-therapy. Citation Format: Jennifer L. Guerriero. Leveraging the complexities of tumor associated macrophages for effective anti-cancer therapy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr SY37-03.